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ANDREA PACE

New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens.

  • Authors: Fortuna, CG; Bonaccorso, C; Bulbarelli, A; Caltabiano, G; Rizzi, L; Goracci, L; Musumarra, G; Pace, A; Palumbo Piccionello, A; Guarcello, A; Pierro, P; Cocuzza, CEA; Musumeci, R
  • Publication year: 2013
  • Type: Articolo in rivista (Articolo in rivista)
  • OA Link: http://hdl.handle.net/10447/88648

Abstract

The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) sidechain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches e FLAP and Amber software e shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained.